Medication adherence has received a great deal of attention over the past several decades; however, its definition and measurement remain elusive. The authors propose a new definition of medication self-management that is guided by evidence from the field of health literacy. Specifically, a new conceptual model is introduced that deconstructs the tasks associated with taking prescription drugs; including the knowledge, skills and behaviors necessary for patients to correctly take medications and sustain use over time in ambulatory care. This model is then used to review and criticize current adherence measures as well as to offer guidance to future interventions promoting medication self-management, especially among patients with low literacy skills.